Novel therapeutic strategies targeting HIV integrase.
BMC Med
; 10: 34, 2012 Apr 12.
Article
em En
| MEDLINE
| ID: mdl-22498430
ABSTRACT
Integration of the viral genome into host cell chromatin is a pivotal and unique step in the replication cycle of retroviruses, including HIV. Inhibiting HIV replication by specifically blocking the viral integrase enzyme that mediates this step is an obvious and attractive therapeutic strategy. After concerted efforts, the first viable integrase inhibitors were developed in the early 2000s, ultimately leading to the clinical licensure of the first integrase strand transfer inhibitor, raltegravir. Similarly structured compounds and derivative second generation integrase strand transfer inhibitors, such as elvitegravir and dolutegravir, are now in various stages of clinical development. Furthermore, other mechanisms aimed at the inhibition of viral integration are being explored in numerous preclinical studies, which include inhibition of 3' processing and chromatin targeting. The development of new clinically useful compounds will be aided by the characterization of the retroviral intasome crystal structure. This review considers the history of the clinical development of HIV integrase inhibitors, the development of antiviral drug resistance and the need for new antiviral compounds.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Integrase de HIV
/
Integrase de HIV
/
Terapia de Alvo Molecular
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
BMC Med
Assunto da revista:
MEDICINA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Canadá